Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study.

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (ß = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (ß = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(ßASRS = 0.51; 95% CI: 0.26;0.77) and (ßSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (ß = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

ADHD in childhood predicts BMI and body composition measurements over time in a population-based birth cohort.

BACKGROUND/OBJECTIVES: Obesity has been reported as an attention-deficit hyperactivity disorder (ADHD) comorbidity. So far, few studies have aimed to explore the potential causal relationship between ADHD and obesity, as well as used other measures of body composition like fat-free mass (FFM) and fat mass (FM) as measures of obesity. This study aimed to test the association between ADHD and body composition (body mass index [BMI] and others) and to evaluate the potential causal relationship with obesity. SUBJECTS/METHODS: Data from the 1993 Pelotas (Brazil) birth cohort at age 11-, 15-, 18-, and 22-year follow-up was used. We performed a cross-lagged panel model (CLPM) analysis between ADHD symptoms and BMI to explore the causal relationship between both traits. Finally, we tested whether ADHD, inattention, and hyperactivity symptom scales were associated with BMI, FM, and FFM at 22 years. RESULTS: In the CLPM, higher ADHD scores at age 11 predicted higher BMI at age 15 (ß = 0.055, 95% CI [0.037; 0.073]). ADHD symptoms at age 11 was also associated with a decrease in the FFM (ß = -0.16, 95% CI [-0.28; -0.05]), and an increase in the BMI (ß = 0.17, 95% CI [0.10; 0.23]) and FM (ß = 0.17, 95% CI [0.06; 0.29]) at 22 years. At 22 years of age, ADHD was associated with FFM and FM. Moreover, an increase in BMI was observed with an increase in several symptoms of ADHD in general (ß = 0.06, 95% CI [0.004; 0.12]), and hyperactivity symptoms (ß = 0.15, 95% CI [0.05; 0.25]). CONCLUSION: ADHD at 11 years predicted a higher BMI at 15 years, and body fat composition in adulthood, suggesting higher scores on ADHD symptoms in early life may be a critical point for body composition in early adulthood. The hyperactivity symptoms may play an important role in the BMI increase.

Sleep duration trajectories from age 3 to 48 months in The Pelotas (Brazil) 2004 Birth Cohort Study.

BACKGROUND: Optimal sleep is essential for child growth, development, and immune function. Few studies have evaluated factors associated with sleep duration in childhood from a longitudinal perspective. OBJECTIVES: This study aimed to identify trajectories of sleep duration in childhood and associated maternal and child characteristics. METHODS: Sleep duration was assessed by maternal report at 3, 12, 24, and 48 months among children from the Pelotas (Brazil) 2004 Birth Cohort. Independent variables included family income, maternal and child demographics, and clinical characteristics. Trajectory analysis was carried out using a semi-parametric, group-based modelling approach. Multinomial logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between independent variables and sleep duration trajectory groups. RESULTS: A total of 3824 participants were included in the analyses. Three trajectories of sleep duration were identified: "short sleepers" (9.1%), "typical sleepers" (72.1%), and "initially longer sleepers" (18.8%). When compared to typical sleepers, children from less schooled mothers (OR 1.82, 95% CI 1.26, 2.62) and those whose mothers reported depressive symptoms during pregnancy (OR 1.31, 95% CI 1.02, 1.68) and consumed alcohol beverages at 3 months post-partum (OR 1.60, 95% CI 1.03, 2.50) were more likely to be short sleepers. Children who shared the bedroom with another child were about 40% (OR 1.41, 95% CI 1.07, 1.87) more likely to be short sleepers. None of the investigated maternal and child characteristics remained associated with the "initially longer sleeper" group. CONCLUSIONS: Among the identified trajectories, the group with short sleep duration trajectory deserves special attention given the importance of adequate sleep duration in the first years of life for the child's growth and development and the high concomitance of other risk factors, such as less schooled mothers, and mothers who reported depressive symptoms during pregnancy and consumed alcohol at 3 months post-partum.

Low neurodevelopmental performance and behavioural/emotional problems at 24 and 48 months in Brazilian children exposed to acetaminophen during foetal development.

BACKGROUND: Several studies have reported that there is an association between developmental and emotional/behavioural problems in children exposed to acetaminophen during foetal development. However, few studies have focused on development and behavioural outcomes in early life. OBJECTIVES: To test the association between prenatal exposure to acetaminophen and low neurodevelopmental performance at 24 months and behavioural/emotional problems at 48 months of life. METHODS: We used data from the 2004 Pelotas Birth Cohort, a population-based longitudinal prospective study. Neurodevelopment was evaluated at 24 months using Battelle's Developmental Inventory (BDI) (n = 3737). We assessed global function as well as each domain (personal-social, adaptative, motor, cognitive, and communication). Behavioural/emotional problems were assessed at 48 months using the Child Behaviour Checklist (CBCL) (n = 3624). We used the CBCL total, externalising, and internalising symptomatology and individual subscales (withdrawn, somatic complaints, anxious/depressed, social problems, cognitive problems, attention problems, aggressive behaviour, and rule-breaking behaviour). Acetaminophen use during pregnancy was retrospectively assessed at the perinatal follow-up. Poisson regression and multiple linear regression analyses were used to test the association, adjusting for several family and maternal sociodemographic and health factors, medication use during pregnancy, and the sex of the child. RESULTS: Acetaminophen exposure during prenatal development was not associated with low neurodevelopmental performance at 24 months assessed using the BDI or to emotional and behavioural problems assessed at 48 months using the CBCL in the adjusted models. CONCLUSIONS: We cannot confirm the existence of an association between acetaminophen used during pregnancy and low neurodevelopmental performance at 24 months and emotional/behavioural problems at 48 months of life based on the present results.

Accelerometer-Derived Sleep Metrics in Adolescents Reveal Shared Genetic Influences with Obesity and Stress in a Brazilian Birth Cohort Study.

We aimed to test the association between sleep-related polygenic scores (PGSs) and accelerometer-based sleep metrics among Brazilian adolescents, and to evaluate potential mechanisms underlying the association through the enrichment of obesity, and cortisol pathway-specific polygenic scores (PRSet). Utilizing data from The 2004 Pelotas (Brazil) Birth Cohort, sleep time window and sleep efficiency were measured at the 11-year-old follow-up using ActiGraph accelerometers. Three sleep-PGSs were developed based on the most recent genome-wide association study (GWAS) of accelerometer-based sleep measures. PRSet, calculated using variants linked to body mass index (BMI) and plasmatic cortisol concentration, aimed to assess pleiotropic effects. Linear regression models, adjusted for sex and the first 10 principal components of ancestry, were employed to explore the impact of sleep-PGS and specific-PRSet on sleep phenotypes. The number of nocturnal sleep episodes-PGS was positively associated with sleep time window (ß =2.306, SE: 0.92, p=0.011). Nocturnal sleep episodes were also associated with sleep time window when restricted to BMI-PRSet (ß=2.682, SE: 0.912, competitive-p=0.003). Both number of sleep episodes and sleep time window cortisol-PRSets were associated (ß=0.002, SE: 0.001, p=0.013; ß=0.003, SE: 0.001, p=0.003, respectively) and exhibited enrichment in molecular pathways (competitive-p=0.011; competitive-p=0.003, respectively) with sleep efficiency. Sleep polygenetic components observed in European adults may partially explain accelerometer-based sleep time window in Brazilian adolescents. Specific BMI molecular pathway strengthened the association between sleep-PGS and sleep time window, while cortisol concentration pathway had a significant impact on the genetic liability for sleep efficiency. Our results suggest genetic overlap as a potential etiological pathway for sleep-related comorbidities, emphasizing common genetic mechanisms.

Mental health from childhood to adolescence predicts excessive weight and body composition at 18 years.

OBJECTIVE: To investigate the association of mental health in childhood and adolescence with four outcomes at 18 years: ultra-processed food (UPF) consumption, body mass index (BMI), excessive weight (EW), and body composition, including fat mass (FM) and fat free mass (FFM) in kg, FM index (FMI) and FFM index (FFMI) in kg/m2. METHODS: Cohort study in which The Development and Well-Being Assessment (DAWBA) (6 and 11 years) and the MINI International Neuropsychiatric Interview (MINI) (18 years) provided information on internalizing (INT), externalizing (EXT) and any mental disorder (ANY). The exposure was classified in: "never", "at 6 and/or 11 years", "at 18 years only" and "at 6, 11, and 18 years". Linear and logistic regression were run. All analyses were stratified by sex. RESULTS: A total of 2722 participants were analyzed. At 18 years, female with EXT disorders at 6 and/or 11 years presented higher BMI (ß: 1.70; 0.18-3.23), FM (ß: 4.74; 1.42-8.06), and FMI (ß: 1.53; 0.28-2.79) than those who never had. The odds of EW at 18 years was also higher in females with EXT disorders at 6 and/or 11 years (OR: 3.39; 1.56-7.36) and at the three time points (OR: 7.08; 1.69-29.59). Males with EXT disorders at 6 and/or 11 years presented higher FM (ß: 4.45; 1.85-7.06) and FMI (ß: 1.47; 0.63-2.31). CONCLUSIONS: Among children and adolescents showing symptoms of EXT disorders, weight should be monitored carefully, thus ultimately contributing to reduce the burden of EW in adolescence.

Insomnia Polygenic Component on Attention Deficit-Hyperactivity Disorder: Exploring this Association Using Genomic Data from Brazilian Families.

Introduction Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. Methods A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Results Insomnia PRS was nominally associated with ADHD (OR = 1.228, p = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Discussion Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.

Gender Division of Housework and Intimate Partner Violence Among Mothers of Toddlers During the COVID-19 Pandemic: Findings from the 2019 Rio Grande (Brazil) Birth Cohort.

During the COVID-19 pandemic, we evaluated the association between gender division of housework and intimate partner violence (IPV) victimization in a population-based cohort of mothers. We collected data on psychological, physical, and sexual IPV using an adapted version of the World Health Organization Violence Against Women instrument and division of housework using a validated questionnaire. We used logistic regression to calculate adjusted odds ratios. We found that in mothers who reported an unequal gender division of housework (higher load), the odds of suffering psychological, physical, or sexual IPV were higher during the first and second years of the pandemic.

Evaluation of genomic factors and early childhood stimulation on intelligence in children from a Brazilian birth cohort: The primary role of independent factors.

BACKGROUND: Childhood cognitive abilities are a predictor of health outcomes and adult income potential. Identifying factors associated with childhood intelligence and their interactions is essential in behavioral research. We assessed the impact of genetic variants and early child stimulation (ECS) on child intelligence and examined their possible interaction as potential modifiers of IQ in a population-based longitudinal study. METHODS: Participants of the 2004 Pelotas Birth Cohort study (N = 4231) underwent intelligent quotient (IQ) by WISC-III assessment at 6 years of age. At 24 and 48-months, mothers answered five ECS marker questions, whose sum was used to create a score. The polygenic score for intelligence (IQ-PGS) was constructed from the GWAS-weighted estimate of cognition. Association was assessed using multiple linear regression models adjusted for maternal, family, and child confounding variables. To explore the possible influence of skin color and ethnoracial classification, the regression models were stratified according to the skin color variable, as a sensitivity analysis. RESULTS: In the adjusted analysis, IQ-PGS (ß = 0.79, 95% confidence interval [95% CI] 0.26;1.31) as well as ECS (ß = 2.34; 95% CI: 1.76;2.92) were associated with IQ in this sample. The association between IQ-PGS and IQ was significant only in the white Brazilian group in the sensitivity analysis. However, there was no interaction between IQ-PGS and ECS on IQ (p(IQ-PGS x ECS) = 0.46). CONCLUSIONS: ECS did not modify the impact of genetic potential on intellectual development during childhood, suggesting that genetic factors and ECS exert independent effects on the IQ levels of children.

Accelerometer-based sleep metrics and gut microbiota during adolescence: Association findings from a Brazilian population-based birth cohort.

BACKGROUND: Sleep and gut microbiota are emerging putative risk factors for several physical, mental, and cognitive conditions. Sleep deprivation has been shown to be linked with unhealthy microbiome environments in animal studies. However, in humans, the results are mixed. Epidemiological studies evaluating the effect of accelerometer-based sleep measures on gut microbiome are scarce. This study aims to explore the relationship between sleep duration and efficiency with the gut microbiota in adolescence. METHODS: A subsample of 352 participants from the 2004 Pelotas (Brazil) Birth Cohort Study with sleep and fecal microbiota data available were included in the study. Sleep duration and sleep efficiency were obtained from actigraphy information at 11 years old whereas microbiota information from fecal samples was collected at 12 years. The fecal microbiota was analyzed via Illumina MiSeq (16S rRNA V3-V4 region) and the UNOISE pipeline. Alpha was assessed in QIIME2. Association measures for sleep variables and microbial α-diversity, and bacterial relative abundance were assessed through generalized models (linear and logistic regression), adjusting for maternal and child variables confounders. RESULTS: Adjusted models showed that sleep duration was positively associated with Simpson index of α-diversity (ß = 0.003; CI95 %: 0.00004; 0.01). Both sleep duration (OR = 0.43; CI95 % 0.25; 0.74) and efficiency (OR = 0.55; CI95 % 0.38; 0.78) were associated with lower Bacteroidetes abundance. CONCLUSION: Our results suggest that sleep duration and efficiency are linked to gut microbiota diversity and composition even with 1-2 years gap from exposure to outcome. The findings support the role of sleep in the gut-brain axis as well as provide insights on how to improve microbiota health.

Hair cortisol measurement: A systematic review of current practices and a proposed checklist for reporting standards.

Summarising hair cortisol concentration (HCC) methodology may provide much-needed data toward protocol standardisation to maximise future comparability of findings across studies. We searched five electronic databases, reviewing 11,716 publications focused on protocols previously used to measure hair cortisol. Our aim was to determine the frequency with which each procedure was reported in the literature. We then conducted a meta-analysis of the HCC results and proposed a checklist for reporting methodological procedures related to HCC. Using pre-selected key terms, we searched for population-based, non-experimental studies reporting HCC outcomes published up to November 2023. Eighty-seven analytical samples were included in the qualitative analysis and 28 in the quantitative analysis. The analyzed studies predominantly included children (≤10 years; 45.4 %) and mainly involved participants from European populations (72.6 %). There was significant variation in hair sample collection procedures across the studies. Most used hair samples up to 3 cm in length (92 %), with around one-third employing either milled (33.3 %) or minced (29.9 %) as grinding methods. For quantification, LC-MS was the most common method (47.1 %), followed by ELISA (24.1 %). Meta-analysis showed significant variability in the mean HCC observed. Meta-regression showed no association between differences in methodology and HCC. In conclusion, the absence of a standardized protocol in HCC research may result in procedural variability, making it difficult to compare findings across studies. Many published studies lacked sufficient detail in describing their methods. To address this, we propose a checklist of reporting guidelines for measurement procedures related to HCC.

Combining cash transfers and cognitive behavioral therapy to reduce antisocial behavior in young men: A mediation analysis of a randomized controlled trial in Liberia.

BACKGROUND: Interventions that combine cognitive behavioral therapy (CBT) with unconditional cash transfers (UCT) reduce the risk of antisocial behavior (ASB), but the underlying mechanisms are unclear. In this paper, we test the role of psychological and cognitive mechanisms in explaining this effect. We assessed the mediating role of executive function, self-control, and time preferences. METHODS: We used data from the Sustainable Transformation of Youth in Liberia, a community-based randomized controlled trial of criminally engaged men. The men were randomized into: Group-1: control (n = 237); and Group-2: CBT+UCT (n = 207). ASB was measured 12-13 months after the interventions were completed, and the following mediators were assessed 2-5 weeks later: (i) self-control, (ii) time preferences and (iii) executive functions. We estimated the natural direct effect (NDE) and the natural indirect effect (NIE) of the intervention over ASB. RESULTS: Self-control, time preferences and a weighted index of all three mediators were associated with ASB scores, but the intervention influenced time preferences only [B = 0.09 95%CI (0.03; 0.15)]. There was no evidence that the effect of the intervention on ASB was mediated by self-control [BNIE = 0.007 95%CI (-0.01; 0.02)], time preferences [BNIE = -0.02 95%CI (-0.05; 0.01)], executive functions [BNIE = 0.002 95%CI (-0.002; 0.006)] or the weighted index of the mediators [BNIE = -0.0005 95%CI (-0.03; 0.02)]. CONCLUSIONS: UCT and CBT lead to improvements in ASB, even in the absence of mediation via psychological and cognitive functions. Findings suggest that the causal mechanisms may involve non-psychological pathways.

The association between maternal fears about their infant/ toddler during the COVID-19 pandemic and depression and anxiety: a birth cohort study.

OBJECTIVE: To assess the association between maternal fears about their infant/toddler and depression and anxiety during the COVID-19 pandemic. METHODS: In 2019, all mothers who gave birth in hospitals in Rio Grande, RS, Brazil were asked to respond to a standardized questionnaire (baseline). We followed them between May-June 2020 (first follow-up point), August-December 2020 (second follow-up point), and from October 2021 to March 2022 (third follow-up point), and asked them if they were: (1) afraid that their infant/toddler would become infected with COVID or get sick (yes/no), (2) afraid that they would contaminate their own child with COVID, and/or (3) worried about the pandemic's effects on their child's future. At baseline and at all follow-up points, we assessed depressive symptoms using the Edinburgh Postnatal Depression Scale and anxiety symptoms using the Generalized Anxiety Disorder Scale, creating symptom trajectories using group-based trajectory modelling. We used multinomial logistic regression to calculate adjusted relative risk ratios (RRR). RESULTS: A total of 1,296 mothers participated. Worrying about the pandemic's effects on their child's future and the fear of contaminating their own child with COVID-19 increased the risk of raising depressive symptoms to a clinical level (RRR = 4.97, 95%CI 2.32-10.64 and RRR = 3.87, 95%CI 1.58-9.47, respectively) and anxiety to a moderate level (RRR = 2.91, 95%CI 1.69-5.01 and RRR = 1.86, 95%CI 1.03-3.35, respectively). CONCLUSION: Fear for their children increased maternal depressive and anxiety symptoms during the pandemic.

The contribution of whole-exome sequencing to intellectual disability diagnosis and knowledge of underlying molecular mechanisms: A systematic review and meta-analysis.

Whole-exome sequencing (WES) is useful for molecular diagnosis, family genetic counseling, and prognosis of intellectual disability (ID). However, ID molecular diagnosis ascertainment based on WES is highly dependent on de novo mutations (DNMs) and variants of uncertain significance (VUS). The quantification of DNM frequency in ID molecular diagnosis ascertainment and the biological mechanisms common to genes with VUS may provide objective information about WES use in ID diagnosis and etiology. We aimed to investigate and estimate the rate of ID molecular diagnostic assessment by WES, quantify the contribution of DNMs to this rate, and biologically and functionally characterize the genes whose mutations were identified through WES. A PubMed/Medline, Web of Science, Scopus, Science Direct, BIREME, and PsycINFO systematic review and meta-analysis was performed, including studies published between 2010 and 2022. Thirty-seven articles with data on ID molecular diagnostic yield using the WES approach were included in the review. WES testing accounted for an overall diagnostic rate of 42% (Confidence interval (CI): 35-50%), while the estimate restricted to DNMs was 11% (CI: 6-18%). Genetic information on mutations and genes was extracted and split into two groups: (1) genes whose mutation was used for positive molecular diagnosis, and (2) genes whose mutation led to uncertain molecular diagnosis. After functional enrichment analysis, in addition to their expected roles in neurodevelopment, genes from the first group were enriched in epigenetic regulatory mechanisms, immune system regulation, and circadian rhythm control. Genes from uncertain diagnosis cases were enriched in the renin angiotensin pathway. Taken together, our results support WES as an important approach to the molecular diagnosis of ID. The results also indicated relevant pathways that may underlie the pathogenesis of ID with the renin-angiotensin pathway being suggested to be a potential pathway underlying the pathogenesis of ID.

The effects of persistent sleep disturbances during early childhood over adolescent ADHD, and the mediating effect of attention-related executive functions: Data from the 2004 Pelotas Birth Cohort.

OBJECTIVE: Investigate effects of persistent sleep disturbances during early childhood over ADHD during the adolescence, and the potential attention-related executive functions mediating this effect. METHODS: We used data from the 2004 Pelotas Birth Cohort. Children's Sleep disturbances were reported by their mothers at 12, 24, and 48 months of age, whereas the Test-of-Everyday-Attention-for-Children (TEA-Ch) and the Development and Well Being Assessment (DAWBA) were applied at 11 years of age to evaluate attention-related executive functions and ADHD, respectively. Persistent sleep problems were defined as reporting have two or more points of difficulty to sleep, nightmares, restless sleeps, and/or <10h/24h sleep duration. Logistic regression and mediation models were used, adjusting for maternal and child sociodemographic, behavior and health related variables. RESULTS: The highest prevalence of adolescent ADHD (15.4%) was on the group who reported having nightmares at 2,4 and 6 years. In adjusted models, we observed an odd of ADHD in the adolescence 2.26 higher in those who reported persistent nightmares (CI95% 1.33, 4.01) compared to those reported transitory or no nightmares. Persistent difficulty to sleep (OR=1.74 CI95% 1.13, 2.66) and restless sleep (OR=1.80, CI95% 1.23, 2.64) during childhood also increased ADHD odds at 11 years. No indirect effect through attention related executive functions was found using mediating models. DISCUSSION: Persistent early sleep disturbances may increase odds of ADHD among adolescents and could be consider as early marker of such disorder, specially nightmares problems. These effects were not mediated by attention-related executive functions. Nevertheless, we had 75% of cohort inception response.

Stress-related genetic components in attention-deficit/hyperactivity disorder (ADHD): Effects of the SERPINA6 and SERPINA1 genetic markers in a family-based brazilian sample.

SERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus-Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying this relationship are still unclear. Evaluation of the SERPINA6/SERPINA1 gene cluster in ADHD may provide relevant information to uncover them. We tested the association between the SERPINA6/SERPINA1 locus, including 95 single nucleotide polymorphisms (SNPs), and ADHD, using data from a Brazilian clinical sample of 259 ADHD probands and their parents. The single SNP association was tested using binary logistic regression, and we performed Classification and Regression Tree (CART) analysis to evaluate genotype combinations' effects on ADHD susceptibility. We assessed SNPs' regulatory effects through the Genotype-Tissue Expression (GTEx) v8 tool, and performed a complementary look-up analysis in the largest ADHD GWAS to date. There was a suggestive association between ADHD and eight variants located in the SERPINA6 region and one in the intergenic region between SERPINA6 and SERPINA1 after correction for multiple tests (p < 0.032). CART analysis showed that the combined effects of genotype GG in rs2144833 and CC in rs10129500 were associated with ADHD (OR = 1.78; CI95% = 1.24-2.55). The GTEx assigned the SNPs as eQTLs for genes in different tissues, including SERPINA6, and the look-up analysis revealed two SNPs associated with ADHD. These results suggest a shared genetic component between cortisol levels and ADHD. HPA dysregulation/altered stress response in ADHD might be mediated by upregulation of corticosteroid binding globulin (CBG, encoded by SERPINA6) expression.

Sleep-related traits and attention-deficit/hyperactivity disorder comorbidity: Shared genetic risk factors, molecular mechanisms, and causal effects.

OBJECTIVES: To evaluate the shared genetic components, common pathways and causal relationship between ADHD and sleep-related phenotypes. METHODS: We used the largest genome-wide association summary statistics available for attention-deficit/hyperactivity disorder (ADHD) and various sleep-related phenotypes (insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype). We estimated the genomic correlation using cross-trait linkage disequilibrium score regression (LDSR) and investigated the potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect was estimated using two-sample Mendelian randomisation (TSMR), using the inverse variance weighted method as the main estimator. RESULTS: A positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD was observed. Insomnia, daytime sleepiness, and snoring shared genes with ADHD, that are involved in neurobiological functions and regulatory signalling pathways. The TSMR supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype. CONCLUSION: Comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors that play an important role in neuronal signalling pathways. A causal effect of sleep disturbances and short sleep duration on ADHD reinforced their role as predictors of ADHD.

Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility.

OBJECTIVES: MicroRNAs (miRNAs) play an important regulatory role in the expression of genes involved in brain functions during development. Genetic variants in miRNA genes may impact their regulatory function and lead to psychiatric disorders. To evaluate the role of genetic variants in genes of miRNAs differentially expressed during neurodevelopment on autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD). METHODS: The miRNAs were identified in the literature. Summary statistics from the most recent genome-wide association studies to date were used to evaluate the association between the selected polymorphisms and each disorder in a look-up approach. In a global analysis, we compared the standardised risk effect of variants in neurodevelopment-related miRNAs with those in the remaining miRNAs from miRBase. RESULTS: The global analysis showed that variants in neurodevelopment-related miRNAs had higher risk effects compared to the other miRNAs for SCZ (p = 0.010) and ADHD (p = 0.001). MIR33B, MIR29B2, MIR29C, MIR137, and MIR135A1 were significantly associated with SCZ, while 55.9% of the miRNAs were at least nominally associated with one or more psychiatric disorders (p < 0.05). CONCLUSIONS: Genetic variants in neurodevelopment-related miRNAs play an important role in the genetic susceptibility of psychiatric disorders, mainly SCZ and ADHD.

Depression in the elderly of a rural region in Southern Brazil. / Depressão em idosos de uma região rural do Sul do Brasil.

The aim of this study is to estimate the prevalence of depression and its associated factors in elderly residents of the rural area of Rio Grande/RS. In this cross-sectional population-based study performed with 994 elderly (≥ 60 years), whose sampling was based on the 2010 Demographic Census, the Patient Health Questionnaire 9 (PHQ-9) was used for Major Depressive Episode (EDM) screening. Descriptive, bivariate and multivariate analyses were performed using logistic regression. The overall prevalence for Major Depressive Episode screening was 8.1%. The variables independently associated with depression were: female gender, continuous use of medications, chronic diseases, body mass index and worse health perception. The creation of programs target at the elderly in the rural area, aimed at screening, early diagnosis of depression and maintenance of treatment, encompassing several factors related to health, are important actions that must be fostered by the health system.

O objetivo deste estudo é estimar a prevalência de depressão e seus fatores associados em idosos residentes da zona rural do município de Rio Grande/RS. Neste estudo transversal de base populacional realizado com 994 idosos (≥ 60 anos), cuja amostragem foi baseada no Censo Demográfico de 2010, utilizou-se o "Patient Health Questionnaire 9" (PHQ-9) para o rastreio de Episódio Depressivo Maior (EDM). Foram realizadas análises descritiva, bivariada e multivariável, com uso de regressão logística. A prevalência geral para o rastreio de Episódio Depressivo Maior foi de 8,1%. As variáveis independentemente associadas com depressão foram: sexo feminino, uso contínuo de medicamentos, doenças crônicas, índice de massa corporal e pior percepção de saúde. A criação de programas de atendimento direcionados aos idosos da área rural, visando rastreamento, diagnóstico precoce de depressão e manutenção do tratamento, englobando diversos fatores relacionados à saúde, são ações importantes que devem ser fomentadas pelo sistema de saúde.

Suicidal thought in southern Brazil: Who are the most susceptible?

BACKGROUND: Suicide is one of the leading causes of death among adolescents and young adults worldwide. However, risk factors for suicidal thoughts might change across cultures and contexts. We aimed to assess the prevalence and associated factors of suicidal thought among adults in a southern Brazilian city. METHODS: This population-based cross-sectional study used a multistage sampling procedure to evaluated individuals with 18 years or more, living in a southern city in Brazil. We collected suicidal thought using a question from the Patient Health Questionnaire-9. In addition, we collected information on sociodemographic, behavioral, and health variables, through a questionnaire using standardized and validated instruments. We calculated prevalence ratios (PR) using Poisson Regression models with robust adjustment of the variance. RESULTS: We collected information from 1295 individuals, 6.6% were positive for suicidal thought. In multivariate analysis, factors independently associated with suicidal thoughts included: being a woman, poor, reporting current tobacco use, having household food insecurity, having three or more morbidities, being in the upper tertile of the stress scores, having had a depression diagnostic in the last year and sadness. LIMITATIONS: We cannot say that the associations found are causal. Suicidal thoughts were assessed from a single question. CONCLUSION: Suicidal thought is a prevalent condition, most likely associated with being a woman, having worst socioeconomic conditions, a poorer health, a higher stress, using tobacco and having depression and/or sadness.